Foreword ix1. Chemoinformatics Theory 1
1.1 Chemoinformatics – What is it? 1
1.2 Chemo- versus Bio-informatics 2
1.3 Scientific Origins 4
1.4 Fundamental Concepts 4
1.4.1 Molecular descriptors and chemical spaces 4
1.4.2 Chemical spaces and molecular similarity 7
1.4.3 Molecular similarity, dissimilarity, and diversity 8
1.4.4 Modification and simplification of chemical spaces 9
1.5 Compound Classification and Selection 11
1.5.1 Cluster analysis 12
1.5.2 Partitioning 13
1.5.3 Support vector machines 16
1.6 Similarity Searching 17
1.6.1 Structural queries and graphs 17
1.6.2 Pharmacophores 18
1.6.3 Fingerprints 21
1.7 Machine Learning Methods 23
1.7.1 Genetic algorithms 23
1.7.2 Neural networks 24
1.8 Library Design 26
1.8.1 Diverse libraries 27
1.8.2 Diversity estimation 28
1.8.3 Multi-objective design 29
1.8.4 Focused libraries 29
1.9 Quantitative Structure-Activity Relationship Analysis 31
1.9.1 Model building 311.9.2 Model evaluation 32
1.9.3 3D-QSAR 33
1.9.4 4D-QSAR 34
1.9.5 Probabilistic methods 35
1.10 Virtual Screening and Compound Filtering 35
1.10.1 Biologically active compounds 35
1.10.2 Virtual and high-throughput screening 36
1.10.3 Filter functions 38
1.11 From Theory to Practice 40
1.11.1 Database design 40
1.11.2 Compound selection for medicinal chemistry 42
1.11.3 Computational hit identification 45
References 47
2. Practice and Products 51
2.1 Accelrys 51
2.2 ACD Labs 59
2.3 Barnard Chemical Information Ltd 67
2.4 BioByte 69
2.5 CambridgeSoft 73
2.6 CAS/Scifinder 80
2.7 ChemAxon 87
2.8 Chemical Computing Group 98
2.9 ChemInnovation Software 103
2.10 ChemNavigator 109
2.11 Chimera-Dock-Zinc from UCSF 112
2.12 Collaborative Drug Discovery (CDD, Inc.) 115
2.13 Daylight 123
2.14 Eidogen-Sertanty (previously Libraria) 127
2.15 Fujitsu Biosciences Group (previously Cache) 137
2.16 Genego 140
2.17 GVK-Bio 144
2.18 Hypercube 148
2.19 IDBS 152
2.20 Infochem 156
2.21 Jubilant Biosys 164
2.22 Leadscope 169
2.23 MDL 171
2.24 Milano Chemometrics and QSAR Research Group 180
2.25 Molecular Discovery 184
2.26 Molecular Networks 187
2.27 Open Eye Scientific Software 194
2.28 Planaria-Software 202
2.29 PubChem 203
2.30 PyMol 208
2.31 RasMol and Protein Explorer 211
2.32 Schrödinger, LLC 215
2.33 Scinova Technologies 223
2.34 Scitegic 226
2.35 Simulation Plus, Inc. 229
2.36 Spotfire 236
2.37 Summit PK 239
2.38 Symyx 243
2.39 TimTec 254
2.40 Tripos 259
SUBJECT APPENDICES
Drug Discovery Informatics Registration Systems
and Underlying Toolkits (Appendices 1 and 2)
Appendix 1 Drug, Molecular Registration Systems, and Chemistry Data
Cartridges 271
Appendix 2 Chemoinformatics Toolkits to Develop Applications 272
Content Databases (Appendices 3–7)
Appendix 3 Compound Availability Databases 273
Appendix 4 SAR Database 273
Appendix 5 Chemical Reaction Databases 274
Appendix 6 Patent Databases 275
Appendix 7 Other Compound and Drug Databases 275
Drug, Molecule, and Protein Visualization (Appendices 8–10)
Appendix 8 Chemical Drawing, Structure Viewing and Modeling Packages 276
Appendix 9 Data Analysis and Mining Tools 276
Appendix 10 Small Molecule – Protein Visualization Tools 277
Modeling and Algorithms (Appendices 11–17)
Appendix 11 Molecular Descriptors 278
Appendix 12 Clogp, Tpsa, and Lipinski Property Calculation Systems 279
Appendix 13 Qsar/Pharmacophore Programs 279
Appendix 14 Docking and Crystallographic Software 280
Appendix 15 Quantum Mechanics Calculations 280
Appendix 16 PK/ADME/Tox Databases and Predictors 280
Appendix 17 Multi-parameter Drug Development/Identification Software 281
Index 283
